Long-term Testosterone Therapy Associated with Improvements in Lipid Levels

An observational study of 255 testosterone-deficient men has found that testosterone therapy reduces total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides while boosting high-density lipoprotein cholesterol (HDL).

The study authors, who published their work in the International Journal of Clinical Practice, also reported significant reductions in systolic and diastolic blood pressure, blood glucose, hemoglobin A1c, C-reactive protein, alanine aminotransferase, and aspartate aminotransferase (p < 0.0001 for all).

“To our knowledge, this is the first study to report on 5-year long-term [testosterone] therapy on cholesterol levels in men with testosterone deficiency,” wrote the authors, who particularly emphasized the LDL numbers. “This finding is of clinical importance since reduction in LDL is thought to correlate with reduced cardiovascular disease risk.”

Subjects in the cumulative registry study, who ranged in age from 33 to 69 (mean 58.02 ± 6.30), all visited a single urologist’s office with concerns about a variety of issues such as erectile dysfunction, decreased libido, or low energy.

Tests found the men to have subnormal plasma total testosterone levels (mean: 9.93 ± 1.37; range: 5.89—12.13 nmol/l) as well as at least mild symptoms of hypogonadism assessed by the Aging Males' symptoms scale.

All men received treatment with parenteral testosterone undecanoate 1000 mg administered at baseline and at 6 weeks, and thereafter every 12 weeks for up to 60 months. All 255 subjects were followed for at least a year. More than half (148) were followed for at least 4 years.

Treatment boosted mean total testosterone levels to about 18 nmol/l within a year (p < 0.0001), where they plateaued for the remainder of treatment.

Total cholesterol levels fell from a mean of 7.3 mmol/l (282 mg/dl) at baseline to about 4.9 mmol/l (188 mg/dl) at 24 months, and then leveled off. LDL levels fell over the same period from 4.2 mmol/l (164 mg/dl) to approximately 2.8 mmol/l (110 mg/dl), while triglycerides fell from approximately 3.1 mmol/l (276 mg/dl) to 2.2 mmol/l (190 mg/dl).

Thanks to a small but significant increase in HDL levels, the ratio of TC/HDL in these treated patients improved over the 2-year period from 5.44 ± 1.61 to 3.49 ± 1.09 and, again, remained constant for the duration of treatment.

Testosterone therapy was also associated with improvements in blood pressure levels. Systolic blood pressure fell from 153.55 ± 17.6 to 137.72 ± 10.9 mmHg (p < 0.0001) over 2 years and then stayed roughly constant. Diastolic blood pressure decreased from 93.49 ± 11.32 to 79.59 ± 7.36 mmHg (p < 0.0001).

Therapy also correlated with improved results on various blood tests.

Fasting blood glucose from 5.74 ± 0.8 mmol/l (103.35 ± 14.42 mg/dl) to 5.41 ± 0.8 mmol/l (97.56 ± 2.35 mg/dl) over 2 years, while hemoglobin A1c fell slowly but consistently. The mean 5-year drop was from 7.06 ± 1.54% to 6.16 ± 1.35%. Markers of liver function improved as well.

As for prostate health, mean prostate volume rose from 28.51 ± 11.2 ml to 30.04 ± 12.35 ml over 3 years, while mean prostate specific antigen increased from 1.77 ± 0.97 to 1.83 ± 0.95 ng/ml (p < 0.0001) with a plateau after 2 years. Three cases of prostate cancer were reported, which was significantly fewer than many existing studies would predict.